Trace Element Status and Free Radical Defense in Elderly Rhesus Macaques (Macaca mulatta) with Macular Drusen

Abstract

Research into the mechanisms underlying the development of age-related macular degeneration (AMD), the leading cause of visual loss in the United States and Europe in people over 60 years old, has been limited in part by the lack of animal models for this disease. In the current study, we examined 62 elderly (≥20 years old) rhesus macaques (Macaca mulatta) for the presence and severity of macular drusen. Drusen were observed in 47% of the macaques; they were similar histologically and in clinical appearance to the drusen observed in humans with AMD. It has been proposed that excessive tissue free radical damage may contribute to the development of AMD. Thus, circulating levels of select components of the free radical defense system and plasma thiobarbituric acid reactive substances (TBARS), an estimate of lipid peroxides, were measured in the above animals. Macaques diagnosed with drusen were characterized by alterations in concentrations and activities of several components of the free radical defense system. Alterations were most evident with respect to those enzymes associated with copper. The concept that excessive oxidative lipid damage might be a factor contributing to the occurrence of this disease is suggested by the findings of higher plasma TBARS concentrations in animals with > 10 drusen compared with animals without drusen.